"There's no bigger, odder, or meaner story in biotechnology today than the gunfight over the disavowal by the journal Nature of an explosive paper on genetic contamination of native Mexican maize by bioengineered corn from the United States." - Biotech's OK Corral

The following article from 'Science and Policy Perspectives' (a publication of the Center for Science, Policy and Outcomes, based in Washington DC) provides an interesting overview of the controversy sparked by the publication of Chapela and Quist's paper.

Of particular interest are the comments made by Alan McHughen, Professor and Senior Research Scientist at the Crop Development Centre at the University of Saskatchewan, Canada. McHughen is the author of 'Pandora's Picnic Basket', a popular guide to GM that argues that many of the concerns about genetic engineering are based in reality on "myths" and "misinformation". McHughen has even claimed, "Opponents to GM put forward untenable pseudo-scientific assertions, then run away, unwilling or unable to defend their positions." McHughen's robust support for genetic engineering is somewhat unsurprising given that McHughen himself is a biotechnologist, seeking to engineer industrial traits into flax.

In that context the following passage in the Science and Policy Perspectives article is particularly striking:

'Another scientist who strongly sides with Chapela is Alan McHughen, a researcher at the Crop Development Center at the University of Saskatchewan in Canada. McHughen is one of those who believe the outburst toward Chapela was far out of proportion to the alleged offense and senses that the attacks on Quist and Chapela were coordinated and conspiratorial. "I think there are a group of people who for whatever reason don't want to hear anything at all about reasons to question the technology," says McHughen. "I read Chapela's paper over and over again and I just couldn't find anything that was inflammatory about it." '

Contrast that with long-time Prakash ally, Wayne Parrott's description of Chapela's paper as "trash" and "indefensible". Or Matt Metz's description of it, "A testimony to technical incompetence". Or fellow Nature letter-writer, Nick Kaplinsky's claim that, "Chapela's name is mud."

Gene flow specialist, Prof Alison Snow of Ohio University is closer to McHughen in her assessment. She argues for the paper's long-term importance, predicting it will lead to a lot more research into the issues raised, "It raises questions that need to be answered. These genes really get around so as far as I'm concerned, let's make sure they are safe and that everyone feels OK about them."

The most laughable claims in the article are those of Wayne Parrott. Parrott denies there has been "any campaign against Chapela" . He even claims the ruckus that followed publication of the paper, was "actually instigated by Chapela himself and raised to a fearful craze by the anti-GM community." According to Parrott, any response by industry "came in response to the din in the press initiated by representatives of the community."

Small problem, Wayne. The attacks launched by the industry's PR machine (courtesy of Murphy, Smetacek and AgBioWorld) didn't follow anything. They were virulent from the first and started immediately, on the very day of publication of Chapela's paper. They were also so detailed as to suggest a significant degree of pre-meditation. The instigators also all had a previous history of such smears and attacks.

And to judge by Wayne Parrott's comments, the campaign goes on!

For more on the industry campaign against Chapela:
http://ngin.tripod.com/deceit_index.html

***
Biotech's OK Corral by Wil Lepkowski
http://www.cspo.org/s&pp/060902.html
Science and Policy Perspectives, No. 13

There's no bigger, odder, or meaner story in biotechnology today than the gunfight over the disavowal by the journal Nature of an explosive paper on genetic contamination of native Mexican maize by bioengineered corn from the United States. Nature published it last November, but by mid-April its editor, Philip Campbell, decided that publishing it was a mistake, said the paper, after all, didn't show what it claimed, and essentially apologized to his readers. Finagling went on for months among reviewers, editors, critics, and the investigators before Campbell made up his mind and finally applied the kibosh.

The episode was infuriating and embarrassing to the authors--microbiologist Ignacio Chapela and his graduate student David Quist of the University of California, Berkeley. But it made Chapela's enemies happy although everyone involved denounced Nature for the way it handled the whole thing. Chapela said something already peer reviewed should have been let alone and left to the usual corrective processes in science, such as letters, rebuttals, and followup work. Those that found fault with Quist and Chapela's work said Nature blundered in accepting a piece of inept science in the first place. Campbell said in various carefully worded statements that Nature did everything carefully, responsibly, and independently, just as it had been doing since its founding in 1869.

Quist and Chapela's paper, "Transgenic DNA Introgressed Into Traditional Maize Landraces in Oaxaca, Mexico," reported that bioengineered corn-in this case Bt corn, a product that kills the corn borer and other pests-- was spreading into native maize varieties in Mexico. Biotech insiders had known what was coming for months because the Mexican government had already disclosed Chapela's results and Chapela was talking about the findings anyway. The country's environment ministry by then had even announced that it had confirmed Chapela's data and a ministry official, Jorge Soberon, called the intrusion "the world's worst case of pollution by genetically engineered crops."

Activitist groups opposed to biotechnology loaded their many Internet list servers and newsgroups with messages of doom come true, offering what to them was compelling reason for the world to renounce genetically modified (GM) crops as assaults on nature. Nature issued its own press releases on the original paper and the opposing letters, upping the media tempo.

Almost as quickly, however, groups of academic plant geneticists began galvanizing their own response, launching technical critiques of Chapela's research and calling into question Chapela's credentials as a scientist. They said he and Quist demonstrated only incompetence by their work, and in the end they successfully pressed Nature into reconsidering its decision to publish it.

Meanwhile, websites sponsored by groups sympathetic to, and supported by, the agricultural biotechnology industry also sprang into action. These groups were led by AgBioWorld, based at Tuskegee University in Alabama and operated by C.S. Prakash, a Tuskegee University plant geneticist who has developed new GM strains of crops such as a high-protein potato.

AgBioWorld (www.agbioworld.com) is the main advocacy machine for GM crops through its listservers to which anyone connected to the Internet can subscribe. It is a forum of sorts that carries news, commentary, and letters supportive of GM crops and tracks the activities of opposition groups, usually to demolish their claims. AgBioWorld carried streams of commentary against Chapela's work and raised suspicions by Chapela and anti-GM groups that a smear campaign had been orchestrated by the biotechnology industry via the pervasive power of the Internet.

Chapela knew what he was getting into, though, and earlier had indications of things to come. In a recent interview with the BBC, he said that he had been pressured by Mexican agricultural interests to lie low with his findings. Contamination of the genes of maize in Mexico constitutes an act of sacrilege as well as criminality there. The agricultural bureaucracy in Mexico is charged with husbanding the native maize and Chapela's work made it apparent that they hadn't been doing their work.

Maize is very special and revered in Mexico. It not only is precious there but is also a global treasure, a 7,000 year-old living bank produced by a combination of hybridization through natural selection and cross-pollination of strains over centuries by peasant farmers. Mexico is more than just a home to maize. It is the shrine. So contamination of these so-called landraces is the reason planting of GM crops or importing GM seeds is a felony in Mexico.

The ban is maddening to the biotech commercial and research interests because it prevents the kind of field research they say they need to do to study gene flow effects of GM plants and test out new strains. This might partly explain the assault on the paper in Nature, but critics seemed to go out of their way to belittle Chapela and Quist, as though programmed to employ a rhetoric that would inflame the world against them and others opposed to biotechnology.

"A testimony to technical incompetence," declared Matthew Metz, a postdoctoral trainee at the University of Washington. Metz is a former but never-friendly colleague of Quist and Chapela at Berkeley and one of the many who sent critical letters to Nature. Said Nick Kaplinsky, a graduate student in Berkeley's Department of Plant and Microbial Biology, "Chapela's name is mud. Anything he tries to do as followup can't be trusted." Wayne Parrott, a plant geneticist at the University of Georgia, said the paper was "trash and indefensible." Academics routinely, in private, rip the work and character of competitors. But the public intensity of these responses seemed to stretch the boundaries of decorum.

What was it that was so dreadfully wrong with their procedures?

The answer isn't simple to articulate because the detection of transgenes in the DNA of plants is no simple subject. But it is important to get the picture more or less right here because the question of what constitutes good science-and how, why, and for what purpose science is done-forms the foundation of the debate. Politics obviously enters-critically-as well, but science nevertheless formed the basis of the whole episode.

The questions range from the way genetic contamination is detected, to the science that is needed to effectively understand what really goes on in plant cells when genes from other organisms (so-called recombinant genes) are introduced, to why one scientist might approach a problem differently from another scientist. Chapela and Quist were attacked on the basis of incomplete technique that formed the basis for incomplete conclusions. But it wasn't as if they hadn't discovered, or confirmed, something critical in gene flow research. They in fact did. The history of science shows that even debatable techniques can throw light upon important new facts that are then followed up by more refined methods. But in this case, the work was carried out in a political crucible.

Quist and Chapela's method was in reality sophisticated but crude. It utilized a technique known-very well known in the research trade-as the "polymerase chain reaction," or PCR, and a related technique, the inverse PCR. Both techniques are almost universally used in genetic research because they amplify by enzymatic multiplication very small amounts of the genetic material a scientist wants to measure. But the method is crude and susceptible to impurities, though it did in fact pick up signs that made evidence of transgression "a good bet," according to Metz.

The aim in this case was to detect not the Bt gene itself (Bt stands for Bacillus thuringiensis, a bacteria whose toxin is deadly to plant pests) but a "marker"-which in this case was a virus called the cauliflower mosaic virus (CMV), which promotes the toxin-producing activity of the gene after it is inserted into the plant. It is the details of facts such as these that make the understanding of biotechnology, at its core, such a difficult but necessary subject for the public to understand if wise outcome-based decisions are to be made. Some controversy happens to surround CMV due to possible untoward malformations of chromosomes that could be transferred across plant lines.

So Quist and Chapela used the PCR technique to show evidence of transgression. But this wasn't enough for the critics and Nature agreed. During those three months or so when the paper was undergoing re-evaluation by a new group of referees, Nature asked Quist and Chapela to verify their results by additional techniques. So they rather hurriedly applied another approach that they said confirmed their earlier results. One referee wasn't convinced, however, and that led Nature to issue its renunciation.

If Quist and Chapela did in fact show enough evidence of transgression, what did they do that was so scientifically criminal?  The answer is that they went too far in their implications. They said that, on the basis of what they had detected through PCR, transgenes had proliferated throughout the maize world in Mexico. It was a really sensational conclusion to those who know something about gene flow as well as to those who want to make a point of their opposition to GM technology.

But all it did on publication was to trigger a barrage of firepower aimed at the authors. One critic of Quist and Chapela who has been especially rough on them is Wayne Parrott. He was also one of those who wrote critical letters to Nature. "I don't think there's been any campaign against Chapela," he says. "Whenever bad science comes out, the system reacts the way it has for hundreds of years. Information gets published and it either stands the test of time or it doesn't."

Parrott believes the ruckus that followed publication of the paper was actually instigated by Chapela himself and raised to a fearful craze by the anti-GM community. Any response by industry, he believes, came in response to the din in the press initiated by representatives of the community, such as the influential activist organizations, Greenpeace, Rural Advancement Foundation International, Union of Concerned Scientists, the Norfolk Genetic Information Network, and the Institute of Science in Society at the Open University in the United Kingdom.

"After all these letters went to Nature," says Parrott, "Chapela turned around and rallied the troops. They said we were mudslinging. They said we were in industry's pocket. They said that we were unethical, and that what we did was totally uncalled for. All that had to have come out of Chapela because anyone who publishes had better be ready to defend what they publish. And he published something that was trash and indefensible.

"The whole thing got out of hand very quickly. And Nature kept sitting on the thing for far more time than they should have. The more time Nature spent on this thing the more time the thing had to roll and gather steam."

To Parrott and other critics, Quist and Chapela depended too much on the PCR technique.  "The polymerase chain reaction," Parrott says, "is used by investigators every single day. We use it because it's fast, sensitive, and reasonably cheap. It's also extremely sensitive to mistakes. So when we do our work, we run a PCR first. Then we take our positive samples and do a more reliable test on them. Chapela used it in its entirety. He could have taken his positive samples and followed them up with something more definitive, such as spraying the things with an herbicide. Or he could have looked for a protein. There are many things he could have done that would have taken maybe a couple more weeks. No one would have questioned it. The thing is that he tried to get into a top journal by using a preliminary test. Then he makes all sorts of claims based on this. He used the wrong enzyme, he used the wrong extraction procedure, everything he did was wrong. And it's not worth the paper it's written on."

One deeply engaged institution in the maize research game is the private, respected, and internationally supported International Maize and Wheat Improvement Center, abbreviated CIMMYT, located near Mexico City. One of CIMMYT's jobs is to track and protect the health of maize and wheat around the world. It was itself stunned by the Quist-Chapela findings.

Shavaji Pandey who heads that center's maize research program says CIMMYT researchers have been unable to repeat Quist and Chapela's results, although the Mexican government has announced that it has detected transgression into several landraces. "I would not say this discredits the paper," he says, "but one of the things that bothers us a lot here is that they found the promoter even in maize varieties that were planted in the field in the mid-70's. This is strange because Bt promoter didn't get into maize until the late 1990s. Chapela was not aware of this discrepancy when he published the paper. Since then, we have brought it to his attention.

"Officially I can't say that transgenic maizes are in Mexico. But I would be surprised if they are not. What is not known is whether Bt transgression into the landraces would have any detrimental effect on the genetic diversity of Mexican maize."

Pandey has found it odd that industry itself has never undertaken the kind of work Chapela instituted, particularly Monsanto, which produces the Bt variety. "A few days ago a few people from Monsanto came to visit," he says, "and I asked them why they didn't spend some money to test the maize collection we have here for transgenic genes through gene flow studies. They heard me and nodded, but I haven't seen any signs that they will be supporting this.

"It's really in their interest. Imagine if Monsanto, Pioneer, and all those other companies appeared on lists of donors participating in genetic diversity, preservation, and things like that. To me, that would do them a lot of good and it might take some of the heat off them."

Pandey remains critical of Chapela but with hardly the venom of Chapela's detractors. "Personally, I am not encouraged by the kind of science he and Quist practiced. I think they could have better handled the results of such a study, since they were dealing with such a controversial issue, instead of jumping around with the comments they made. If I had been them I would have double checked and triple checked those results with students of other methodologies and maybe even some other labs before I would have made the kinds of comments they made."

Chapela and Quist do have their boosters, or at least friendly colleagues. One is Allison Snow of Ohio State University. Her field is gene flow and, with a reservation or two, she is sympathetic toward Chapela's data. "I don't think the science in the second half of their paper was very good," she says. "They said there were multiple insertions of transgenes, where they were going in the genome wasn't predictable, and that therefore that there was something scary about transgenes.

"But the first half of the paper, while you could always have asked them to do a better job, I thought was well supported. And anyway, a lot of people already believe that transgression has already happened and the Mexican government has confirmed it and talked about it in several news releases. What was interesting was Chapela's positive control with the grain from the local store. That had been shipped in from the United States as animal feed and was definitely transgenic. It was not for human consumption but people are planting it. So there are all those different parts to this puzzle."

Snow thinks the ferocity of opposition to Chapela came partly out of the vileness of the polarized politics around biotechnology and the personalities involved. Quist and Chapela had opposed a $25 million cooperative research deal reached in 1998 between Novartis, a plant biotech corporation, and Berkeley's department of microbial and plant biology. Both Kaplinsky and Metz were part of that department during the height of the debate. Additionally, Quist was accused (falsely, he says) of destroying some transgenic fieldwork Kaplinsky had been conducting. So the authors and their critics had a long history of antagonism before publication of the paper.

Snow, who has the respect of both sides, says personal politics could easily have stirred the intense feelings around the paper, but that the issues were wider. "The things they said could have been taken as a threat to the field of ag biotechnology," she says, "because all along the ag biotechnologists have been saying that we know what these genes do, they're just like other genes, they're inherited just like any Mendelian gene. Although sometimes there may be a few problems, it's not like they're jumping all around the genome in an unpredictable way. So they got very worried about the statements Chapela was making. They felt what he was saying wasn't very well supported and that just got people furious. It's all very polarized.

"What I thought was most interesting was that the transgenes are novel genetic markers that show the flow of genes from modern crop varieties into landraces. It shows you how connected the crop is to the landrace. And that's one reason I think Nature agreed to publish it in the first place. Anytime you have a transgene, it's a marker that is new. And that shows that this is going on all the time. We just didn't really know about it. The second question of course is what difference does it make? It wasn't legal being there.

"So on the whole, people attacked the whole the paper, but sort of forgot that the first half of it was probably correct. It's going to make people study this a whole lot more and thus it's going to have a good effect in the long run. It raises questions that need to be answered. These genes really get around so as far as I'm concerned, let's make sure they are safe and that everyone feels OK about them."

Norman C. Ellstrand, a genetics professor who studies gene flow in various crops at the University of California, Riverside, served with Chapela on a panel that produced in February a report on regulating GM crops. Ellstrand believes that an important truth is missing from the Wagnerian furies over the Chapela paper. "Once you have genes that have entered a population," he says, "they will remain in the population unless something else happens. Let's say that five percent of the landraces have transgenes in them. Then you might expect that based on population genetics rules, they will remain at five percent even if no more transgenes are added to the population. There are some policy people saying that if you don't add any more they will go away. But that's not true.

"If they are neutral they will remain at five percent. And if they are beneficial to the plant they will increase in frequency. If they are a detriment to the plant, then natural and human selection would pull them out of the population and they would go down in frequency. If there were constant gene flow coming into the population from an external source, then we would expect that the transgenes would stay there forever, whether detrimental, positive, or neutral. These are some implications people have avoided talking about.

"So now, because of Quist and Chapela's work, we now have a gene that demonstrates that external gene flow has occurred in these landraces. Am I worried about these particular transgenes? No. But what I do worry about is that if genes can move a great distance into very remote areas relatively quickly, what is to keep genes that are being put into corn these days to create industrial compounds from doing the same thing? These are plants that are made to be chemical factories, and manufacture compounds, like drugs, that would be sold to the biomedical community. Many such proteins are coming down the pike. If these are genes that create toxic compounds then we have problems. And that's been my read on this from the start."

Another scientist who strongly sides with Chapela is Allan McHughen, a researcher at the Crop Development Center at the University of Saskatchewan in Canada. McHughen is one of those who believe the outburst toward Chapela was far out of proportion to the alleged offense and senses that the attacks on Quist and Chapela were coordinated and conspiratorial. "I think there are a group of people who for whatever reason don't want to hear anything at all about reasons to question the technology," says McHughen. "I read Chapela's paper over and over again and I just couldn't find anything that was inflammatory about it.

"I guess if I have an issue with anybody, it is with Nature and the way they handled the whole thing. Even if it had been done poorly, the fact is that they accepted it, they reviewed it, and they published it using presumably fair, reasonably consistent criteria. Once it's done and there's data that alter those findings, they publish those data and let the authors of new papers present their data in contrast. So that's my biggest issue and I think Nature is most at fault here. Also, I think Nature itself likes the media attention it gets over controversial stories that have significant consequences. So there's a bit of self-serving going on here."

Metz, one of the critics, doesn't like the position he has been placed in by the anti GM forces. "Right now, I'm lumped into the role of corporate phantom, which I find to be entirely bogus," he says. "They talk about ecology and holism and they disparage reductionism. And yet they do their study in the most clumsy reductionist fashion. They didn't even show that what they detected was in the actual genome of the corn. They just show that it's in their DNA samples. You look at the wide variety of problems in that work and it's just incredible that they could have messed up so profoundly."

To him, a conspiracy did apparently exist and Nature fell victim to it. But Nature of course denies that any outside pressure determined how it acted in the end. It's editor, Philip Campbell, says he responded to objections to the paper in the best way he could: to hear the objections, give Quist and Chapela a chance to gather new data, then make an independent judgment over the paper.

Following a series of letters on the episode published in the June 27 issue of the journal, he said, "It is highly unusual for Nature to publish a paper whose principal conclusion is shown to be not necessarily false but unsustainable on the basis of the reported evidence. The paper was not formally retracted by its authors or by Nature. In the circumstances, Nature considered it appropriate for the record to make clear to readers its revised view of its original decision to publish." Then he reasserted Nature's "vows of independence" from "partisan anti- or pro-technology agendas and from commercial interests."

That didn't quite answer why Nature considered the Quist-Chapela paper so out of the ordinary that extraordinary measures needed to be taken. Whether the experience with the Quist-Chapela paper signifies some new editorial policy change within Nature is almost impossible to assess and Nature indicates nothing has really changed in the way it evaluates, edits, and reviews submissions. "Ever since its launch in 1869," Campbell says, "Nature has made its own editorial and scientific judgements on the basis of advice from referees (who quite often, as in this case, make differing recommendations). That is what we did here."

Was there, however, an academic-industrial conspiracy? Metz doesn't think so. He, along with Kaplinsky, says he doesn't go along with everything industry aims for. He says he just wants to see good science done. The GM opposition objects to the heavy-handedness of the attacks on Chapela, especially the use of the Internet to spread the rhetorical bile. What they most objected to was the use of apparently fictitious names on the AgBioWorld listservers to disparage Quist and Chapela. They believe Monsanto, with the help of The Bivings Group, a marketing organization that specializes in the use of the Internet to win public relations efforts, was behind the campaign.

To Chapela, who speculates frequently on the character and sociology of the scientific enterprise itself, the lessons are meaningful. "It's interesting how this whole event has really split the profession of biology," he says. "There are people who don't see anything valuable in this study. Kaplinsky called it trivial and obvious. And on the other hand you have the group of people who say this is a very significant discovery.

"All this goes to the root of what we consider science, how technique, technology, and science are so perilously mixed. I think it is very clear that this has been built now as a case study of why it is that we don't have an academic, scientific establishment that should be able to provide independent and really objective opinion. We do not have that. The moment you ask the wrong questions or come up with the 'wrong' answer the standards of proof and questioning are raised incredibly, to the point that nobody could have made this kind of discovery without being challenged."

Quist attributes the response to two phenomena. "One is the locally-brewed paranoia concocted over the bitter and still simmering debate over the implementation of the Novartis deal with the Plant and Microbial Biology Department. Everyone still has indigestion over that.

"The second comes from a larger paranoia, perhaps a deep and unsettled knowledge in the backs of their minds that even though biotechnology holds promise, there is a dark underbelly of recombinant-DNA technology that they don't want to expose. That is, the unstable and unpredictable behavior of rDNA during initial transformation and subsequent inheritance of those genes in future generations. These people are experts on this stuff, and the fact that they are so dismissive of the inherent dangers of their work is puzzling to me."

Quist says that if he were to do it all over again, "We probably would not have included exploratory data that wasn't rock solid, even if it did suggest a very interesting pattern of transgene movement and rearrangement. Our thinking in publishing these results was that, well sure, it would be criticized. But if investigators were truly interested in the biological or ecological significance of their data, they would spend time trying to verify it rather than resorting to malicious attacks and subterfuge. Where we really came under assault was in elaborating the potential evolutionary and ecological significance of this finding. For the biotech industry it represents an enormous PR disaster. It undermines their efforts to convince the world that their science is a very exact and controllable one."

So all this may not end up being just a minor episode in the war over whether genetic modification of crops is a good thing for the world. Much depends on the influence Chapela's work has in the gene flow community, which will in the end determine whether biotechnology finds a solid, global place in agriculture. Right now things don't look good for the industry because of bad public relations and also because of the innate idea that fooling around in any technological way with the genetic character of life of any kind is too spooky to hail. Then, too, if it is determined scientifically that proliferation of transgenes is a common rogue event, the curtain could ring down on the technology.

At the root of the controversy is, of course, the science of genetics and gene flow, plus the incessant arguments over whether GM crops in the long run will really alleviate hunger and poverty in poor countries with rising populations, and add to the sustainability of agriculture by reducing chemical inputs and land use.  The promise is alluring, but right now it is backed mostly by hope, hype, and a lot of noise.

Meanwhile, the GM forces are saying don't worry, trust science and thus trust us. Opposition groups from Greenpeace activists to working organic farmers would rather just see the whole troubled and troubling biotechnology enterprise go away. The industry spends most of its time defending what it does behind science while at the same time creating suspicion by opposing any legislative moves to label their products as genetically modified. Trust seems to be the quality most abused and least detectable in the field of biotechnology and all one can see on the horizon is continuing conflict and trouble.